rs6570989

Variant names:

• chr6-101509537-G-A
• rs6570989
• NM_021956.5:c.115+110145G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-101509537-G-A
• chr6-101509537-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021956.5(GRIK2):​c.115+110145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,004 control chromosomes in the GnomAD database, including 6,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6038 hom., cov: 32)
• Consequence: GRIK2 NM_021956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 3 publications found

Genes affected

GRIK2 (HGNC:4580): (glutamate ionotropic receptor kainate type subunit 2) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing at multiple sites within the first and second transmembrane domains, which is thought to alter the structure and function of the receptor complex. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. Mutations in this gene have been associated with autosomal recessive cognitive disability. [provided by RefSeq, Jul 2008]

GRIK2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• intellectual disability, autosomal recessive 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder with impaired language and ataxia and with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIK2	NM_021956.5	c.115+110145G>A		intron_variant	Intron 2 of 16	ENST00000369134.9	NP_068775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIK2	ENST00000369134.9	c.115+110145G>A		intron_variant	Intron 2 of 16	5	NM_021956.5	ENSP00000358130.6

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38348 AN: 151886 Hom.: 6038 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38360 AN: 152004 Hom.: 6038 Cov.: 32 AF XY: 0.260 AC XY: 19301 AN XY: 74296

African (AFR) AF: 0.399 AC: 16547 AN: 41428

American (AMR) AF: 0.215 AC: 3279 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2470 AN: 5170

South Asian (SAS) AF: 0.417 AC: 2009 AN: 4818

European-Finnish (FIN) AF: 0.236 AC: 2495 AN: 10568

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10438 AN: 67972

Other (OTH) AF: 0.220 AC: 464 AN: 2112

Alfa AF: 0.196 Hom.: 1925

Bravo AF: 0.254

Asia WGS AF: 0.430 AC: 1489 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6570989; hg19: chr6-101957413;